A randomized comparison of a commercially available portion-controlled weight-loss intervention with a diabetes self-management education program.

OBJECTIVE: This study examined the efficacy of a commercially available, portion-controlled diet (PCD) on body weight and HbA1c over 6 months in obese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: One-hundred participants with a mean±s.d. age of 55.6±10.6 year, body weight of 102.9±18.4 kg and HbA1c of 7.7±1.3% were randomly assigned to a 9-session group lifestyle intervention that included a PCD or to a 9-session group program of diabetes self-management education (DSME). Participants in the two groups were prescribed the same goals for energy intake (1250-1550 kcal per day) and physical activity (200 min per week). RESULTS: While both groups produced significant improvements in weight and HbA1c after 6 months of treatment, PCD participants lost 7.3 kg [95% confidence interval (CI): -5.8 to -8.8 kg], compared with 2.2 kg (95% CI: -0.7 to -3.7 kg) in the DSME group (P<0.0001). Significantly more PCD than DSME participants lost 5% of initial weight (54.0% vs 14.0%, P<0.0001) and 10% (26.0% vs 6.0%, P<0.0001). HbA1c declined by 0.7% (95% CI: -0.4 to -1.0%) in the PCD group, compared with 0.4% (95% CI: -0.1 to -0.7%) in DSME (P<0.026). Across both groups, larger weight losses were associated with greater reductions in HbA1c (r=0.52, P<0.0001). CONCLUSIONS: These findings demonstrate that a commercially available portion-controlled meal plan can induce clinically meaningful improvements in weight and glycemic control in obese individuals with type 2 diabetes. These data have implications for the management of obesity in primary care, as now provided by the Centers for Medicare and Medicaid Services.

Atrial fibrillation precipitated by carotid sinus massage in a patient with unexplained syncope.

BACKGROUND: Carotid sinus massage (CSM) is a useful tool in the investigation of unexplained syncope, but is associated with risks. AIM: To describe the first reported case of atrial fibrillation precipitated by CSM during the investigation of a patient with recurrent unexplained syncope. RESULTS: A 58-year-old female underwent CSM as part of a tilt test protocol for the investigation of recurrent unexplained syncope. Left CSM revealed the diagnosis of mixed cardioinhibitory and vasodepressor carotid sinus syndrome but also precipitated atrial fibrillation, an arrhythmia previously unreported as a complication of the procedure. CONCLUSIONS: CSM is a useful tool in the investigation of patients with recurrent unexplained syncope, but may cause atrial fibrillation in addition to other previously described complications and should, therefore, be used with caution.

Chromosome-wide distribution of haplotype blocks and the role of recombination hot spots.

Recent studies of human populations suggest that the genome consists of chromosome segments that are ancestrally conserved ('haplotype blocks'; refs. 1-3) and have discrete boundaries defined by recombination hot spots. Using publicly available genetic markers, we have constructed a first-generation haplotype map of chromosome 19. As expected for this marker density, approximately one-third of the chromosome is encompassed within haplotype blocks. Evolutionary modeling of the data indicates that recombination hot spots are not required to explain most of the observed blocks, providing that marker ascertainment and the observed marker spacing are considered. In contrast, several long blocks are inconsistent with our evolutionary models, and different mechanisms could explain their origins.

Carbon dioxide, critical closing pressure and cerebral haemodynamics prior to vasovagal syncope in humans.

The cerebrovascular changes that occur prior to vasovagal syncope (VVS) are unclear, with both increases and decreases in cerebrovascular resistance being reported during pre-syncope. This study assessed the cerebrovascular responses, and their potential underlying mechanisms, that occurred before VVS induced by head-up tilt (HUT). Groups of 65 normal subjects with no previous history of syncope and of 16 patients with recurrent VVS were subjected to 70 degrees HUT for up to 30 min. Bilateral middle cerebral artery (MCA) cerebral blood flow velocities (CBFVs) were measured using transcranial Doppler ultrasound, along with simultaneous measures of MCA blood pressure, heart rate, and end-tidal and transcutaneous carbon dioxide concentrations. All 16 patients and 14 of the control subjects developed VVS during HUT. During pre-syncope, mean CBFV declined, due predominantly to a decrease in diastolic rather than systolic CBFV (decreases of 44.5+/-19.8% and 6.3+/-12.9% respectively; P<0.0001). CO(2) levels and indices of cerebrovascular resistance decreased during pre-syncope, while critical closing pressure (CrCP) increased to levels approaching MCA diastolic blood pressure before decreasing precipitously on syncope. Pre-syncopal changes were similar in syncopal patients and syncopal controls. CrCP, therefore, rises during pre-syncope, possibly related to progressive hypocapnia, and may account for the relatively greater fall in diastolic CBFV. Falls in cerebrovascular resistance, therefore, may be offset by rises in CrCP due to hypocapnia, leading to diminished cerebral blood flow during pre-syncope.

Cerebral autoregulatory responses to head-up tilt in normal subjects and patients with recurrent vasovagal syncope.

BACKGROUND: The effect of orthostatic stress on dynamic cerebral autoregulation (CA) in normal subjects and patients with recurrent vasovagal syncope (VVS) is unclear. This study assessed the dynamic CA responses of both groups to head-up tilt. METHODS AND RESULTS: Seventeen patients with recurrent VVS and 17 pair-matched control subjects underwent 70 degrees head-up tilt for up to 30 minutes. Bilateral middle cerebral artery blood flow velocities (CBFV) were measured with transcranial Doppler ultrasound along with noninvasive beat-to-beat blood pressure (BP), heart rate, and transcutaneous and end-tidal CO(2) concentrations. Indices of dynamic CA were derived for periods before, during, and after tilt. Eight normal subjects who developed VVS in an identical protocol but who had no previous clinical history of syncope were also studied. CBFV and transcutaneous and end-tidal CO(2) levels declined significantly during head-up tilt in all groups (P<0.0001). Dynamic CA indices were unchanged throughout tilt in nonsyncopal control subjects and were initially unchanged in patients but deteriorated significantly in patients and syncopal control subjects in the minutes before (P=0.027 and P=0.012, respectively) and after (P=0.002 and P=0.007, respectively) syncope. CONCLUSIONS: Dynamic CA is preserved in patients and control subjects initially after head-up tilt. Autoregulatory function remains intact in nonsyncopal control subjects during prolonged orthostasis but deteriorates in patients and syncopal control subjects immediately before and after VVS.

A case of arrhythmia-induced transient cerebral hyperaemia.

Transient cerebral hyperaemia following an arrhythmia has not been previously demonstrated in humans. We report the effects of head-up tilt on a 78-year-old man with neurocardiogenic syncope. During tilt, an asymptomatic arrhythmia caused arterial blood pressure and transcranial Doppler-recorded cerebral blood flow velocity to fall markedly. Upon spontaneous resumption of sinus rhythm, cerebral blood flow velocity increased to values greater than those prior to the arrhythmia. This occurred prior to a full recovery of arterial blood pressure, indicating spontaneous transisent hyperaemia. Pressure-flow velocity graphs support current methods of measuring critical closing pressure and demonstrate a rise in critical closing and a fall in resistance-area product after the arrhythmia.

A study to evaluate serum and urinary hormone levels following short and long term administration of two regimens of progesterone cream in postmenopausal women.

OBJECTIVE: To determine the pharmacokinetics of a progesterone cream following short and long term dermal administration. DESIGN: Single-centre, randomised, multiple-dose, open-label study. SETTING: Reproductive Medicine Trust, London. POPULATION: Twenty-four healthy postmenopausal women aged between 40 and 65 years were recruited through an advertisement in a local newspaper. METHODS: The women were randomly allocated to progesterone cream 40 mg daily or 20 mg, twice daily, for 42 days. MAIN OUTCOME MEASURES: The concentration of progesterone in the serum was measured on days 1 and 42 before the morning dose, and at 2, 4, 6, 12 and 24 hours after the morning dose. Serum follicle stimulating hormone, oestradiol, testosterone and urinary pregnanediol-3-glucuronide were also measured on days 1 and 42. RESULTS: Three subjects dropped out before using the cream and two more dropped out after the first treatment leaving a reportable sample of 19 women. There was a rise in the mean progesterone concentration at each sampling time between days 1 and 42. There was evidence of a rise in pregnanediol-3-glucuronide over the course of the study. There was no change in follicle stimulating hormone, oestradiol or testosterone. There was no difference between the two regimens. CONCLUSIONS: Transdermal progesterone (40 mg) per day for 42 days causes a small increase in serum progesterone concentration, although there is wide variation. Whether such levels are of clinical benefit remains to be seen.

Dynamic cerebral autoregulation is unaffected by aging.

BACKGROUND AND PURPOSE: Normal aging is associated with marked changes in the cardiovascular and cerebrovascular systems. Although cerebral autoregulation (CA) is impaired in certain disease states, the effect of age per se on dynamic CA in humans is unknown and the focus of this study. METHODS: Twenty-seven young subjects (/=55 years), matched for sex and systolic blood pressure (BP), underwent measurement of cerebral blood flow velocity by transcranial Doppler ultrasound and noninvasive beat-to-beat arterial BP measurement during induced and spontaneous dynamic BP stimuli. A standard dynamic autoregulatory index (ARI) was derived for each spontaneous and induced dynamic BP stimulus to include the step response, as well as cardiac baroreceptor sensitivity (BRS), for the 2 groups. RESULTS: The mean age of the young group was 29+/-5 years, and that of the older group was 68+/-5 years. Cardiac BRS was reduced in the older group (8. 6+/-4.5 versus 16.9+/-8.8 ms/mm Hg; P:<0.0001). However, no age-related differences were demonstrated in step response plots or in ARI values for any pressor or depressor dynamic BP stimulus (P:=0. 62), with mean ARI values for all stimuli combined being 4.9+/-1.8 for the young group and 5.0+/-2.3 for the older group. CONCLUSIONS: Although increasing age is associated with a decrease in cardiac BRS, dynamic CA, as assessed by step response analysis as well as cerebral blood flow responses to transient and induced BP stimuli, is unaffected by aging.

The radioprotective effects of WR-2721 on radiation-induced goblet cell loss.

We assessed the efficacy of the radioprotective effects of WR-2721 in radiation-induced goblet cell loss. Fourteen female New Zealand white rabbits were divided into radioprotected, radiounprotected, and control groups. Ten rabbits received 5,000 rad of beta irradiation to the temporal conjunctiva of both eyes. The right eyes were pretreated with topical applications of WR-2721 30 minutes and 1 minute before irradiation. The left eyes received irradiation only. Four additional rabbits received neither irradiation nor pretreatment with WR-2721. After a 2-month waiting period, each animal was killed and goblet cell densities per high-power field (GCD/HPF) were determined over the areas in question and compared using paired sample t tests. The mean GCD/HPF for the radioprotected, unprotected, and control groups were 10.93, 4.68, 23.15 (right eye), and 26.25 (left eye). Paired sample t tests showed a significant radioprotective effect when comparing WR-2721-treated animals with those receiving radiation only (p less than 0.003). Independent sample t tests showed significant goblet cell loss in both the radioprotected (p less than 0.018) and radiounprotected eyes (p less than 0) when compared with control groups. These data suggest a radioprotective effect of WR-2721 in radiation-induced goblet cell loss.

The effects of pause time on auditory comprehension of language-disordered children.

Language-disordered children were presented with two types of commands in a sentence comprehension task. One 3-sec pause was placed at the same syntactic boundary in one-half of the sentences in Set I and Set II. Results indicate that the subjects' performance improved as a function of the pause in Sentence Set II but not in Sentence Set I.